Canagliflozin, an SGLT2 inhibitor, corrects glycemic dysregulation in TallyHO model of T2D but only partially prevents bone deficits.
Canagliflozin, an SGLT2 inhibitor, corrects glycemic dysregulation in TallyHO model of T2D but only partially prevents bone deficits.
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DOI：
10.1016/j.bone.2020.115625
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发表时间：
2020-12
期刊：
影响因子：
4.1
通讯作者：
Nyman JS
中科院分区：
文献类型：
--
作者：
Thrailkill KM;Bunn RC;Uppuganti S;Ray P;Popescu I;Kalaitzoglou E;Fowlkes JL;Nyman JS
2型糖尿病（T2 D）骨折风险较高归因于骨的微观结构和材料特性的疾病特异性缺陷，尽管主要原因尚未确定。TallyHO（TH）小鼠是一种早发性T2 D和肥胖症的多基因模型，类似于人类青春期发病的T2 D。由于表型的不完全转化，约25%的雄性TH小鼠从未发生高血糖症，提供了品系匹配的非糖尿病对照。利用这种T2 D模型，我们研究了卡格列净（CANA）降糖治疗对糖尿病骨的影响。从约8至20周龄监测具有或不具有高血糖症（高BG、低BG）的雄性TH小鼠，并与从约8至20周龄用CANA处理的年龄匹配的雄性TH小鼠进行比较。在20周时，具有高血糖[高血糖：687±106 mg/dL]的未治疗TH小鼠表现出较低的体重，股骨皮质骨减少（横截面积和厚度减小;孔隙度增加）和股骨干骺端和L 6椎骨的松质骨中（骨体积分数、厚度和组织矿物质密度降低），以及当与具有低BG的未处理TH小鼠相比时皮质骨和椎骨强度的降低（降低的屈服力和极限力）[低BG：290±98 mg/dL; p<0.0001]。CANA治疗在代谢方面是有利的，使体重、BG和HbA 1c正常化至与低BG组相当的值。随着药物诱导的血糖改善，CANA组的皮质面积和厚度显著高于高血糖组，但CANA组的强度缺陷持续存在，屈服力和屈服应力较低（部分与骨几何形状无关）。此外，CANA仅部分预防了T2 D相关的骨小梁体积分数损失。综上所述，这些发现表明CANA降低葡萄糖和正常血糖控制的能力改善了糖尿病性骨病，但并不完全。
Higher fracture risk in type 2 diabetes (T2D) is attributed to disease-specific deficits in micro-structural and material properties of bone, although the primary cause is not yet established. The TallyHO (TH) mouse is a polygenic model of early-onset T2D and obesity analogous to adolescent-onset T2D in humans. Due to incomplete penetrance of the phenotype, ~25% of male TH mice never develop hyperglycemia, providing a strain-matched, non-diabetic control. Utilizing this model of T2D, we examined the impact of glucose-lowering therapy with canagliflozin (CANA) on diabetic bone. Male TH mice with or without hyperglycemia (High BG, Low BG) were monitored from ~8 to 20 weeks of age, and compared to age-matched, male, TH mice treated with CANA from ~8 to 20 weeks of age. At 20 weeks, untreated TH mice with high BG [High BG: 687±106 mg/dL] exhibited lower body mass, decrements in cortical bone of the femur (decreased cross-sectional area and thickness; increased porosity) and in trabecular bone of the femur metaphysis and L6 vertebra (decreased bone volume fraction, thickness, and tissue mineral density), as well as decrements in cortical and vertebral bone strength (decreased yield force and ultimate force) when compared to untreated TH mice with low BG [Low BG: 290±98 mg/dL; p<0.0001]. CANA treatment was metabolically advantageous, normalizing body mass, BG and HbA1c to values comparable to the Low BG group. With drug-induced glycemic improvement, cortical area and thickness were significantly higher in the CANA than in the High BG group, but deficits in strength persisted with lower yield force and yield stress (partially independent of bone geometry) in the CANA group. Additionally, CANA only partially prevented the T2D-related loss in trabecular bone volume fraction. Taken together, these findings suggest that the ability of CANA to lower glucose and normalized glycemic control ameliorates diabetic bone disease but not fully.
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DOI：
10.1007/s00198-016-3614-7
发表时间：
2016-09
期刊：
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
影响因子：
--
作者：
Heilmeier U;Cheng K;Pasco C;Parrish R;Nirody J;Patsch JM;Zhang CA;Joseph GB;Burghardt AJ;Schwartz AV;Link TM;Kazakia G
通讯作者：
Kazakia G
影响因子：
16.2
作者：
TODAY Study Group
通讯作者：
TODAY Study Group
糖尿病状况，HBA1C，糖尿病持续时间，微血管疾病以及远端半径和胫骨的骨质质量与高分辨率外周定量计算机断层扫描术测量。
DOI：
10.1007/s00198-018-4678-3
发表时间：
2018-12
期刊：
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
影响因子：
--
作者：
de Waard EAC;de Jong JJA;Koster A;Savelberg HHCM;van Geel TA;Houben AJHM;Schram MT;Dagnelie PC;van der Kallen CJ;Sep SJS;Stehouwer CDA;Schaper NC;Berendschot TTJM;Schouten JSAG;Geusens PPMM;van den Bergh JPW
通讯作者：
van den Bergh JPW
影响因子：
4
作者：
Kim, Jung Han;Stewart, Taryn P.;Naggert, Jurgen K.
通讯作者：
Naggert, Jurgen K.
影响因子：
5.8
作者：
Burghardt, Andrew J.;Issever, Ahi S.;Link, Thomas M.
通讯作者：
Link, Thomas M.